chr7-33015703-C-T

Variant names:

• chr7-33015703-C-T
• rs72555746
• NM_001002010.5:c.861G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001002010.5(NT5C3A):​c.861G>A​(p.Glu287Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,610,512 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (77 hom.)
• Consequence: NT5C3A NM_001002010.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0450
• Publications: 5 publications found

Genes affected

NT5C3A (HGNC:17820): (5'-nucleotidase, cytosolic IIIA) This gene encodes a member of the 5'-nucleotidase family of enzymes that catalyze the dephosphorylation of nucleoside 5'-monophosphates. The encoded protein is the type 1 isozyme of pyrimidine 5' nucleotidase and catalyzes the dephosphorylation of pyrimidine 5' monophosphates. Mutations in this gene are a cause of hemolytic anemia due to uridine 5-prime monophosphate hydrolase deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and pseudogenes of this gene are located on the long arm of chromosomes 3 and 4. [provided by RefSeq, Mar 2012]

NT5C3A Gene-Disease associations (from GenCC):

• hemolytic anemia due to pyrimidine 5' nucleotidase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 7-33015703-C-T is Benign according to our data. Variant chr7-33015703-C-T is described in ClinVar as Benign. ClinVar VariationId is 780675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.045 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00403 (614/152296) while in subpopulation SAS AF = 0.0302 (146/4832). AF 95% confidence interval is 0.0262. There are 4 homozygotes in GnomAd4. There are 328 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002010.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3A	NM_001002010.5	MANE Select	c.861G>A	p.Glu287Glu	synonymous	Exon 8 of 9	NP_001002010.2	X6RM59
	NT5C3A	NM_001374335.1		c.762G>A	p.Glu254Glu	synonymous	Exon 7 of 8	NP_001361264.1
	NT5C3A	NM_001002009.3		c.759G>A	p.Glu253Glu	synonymous	Exon 9 of 10	NP_001002009.1	Q9H0P0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3A	ENST00000610140.7	TSL:1 MANE Select	c.861G>A	p.Glu287Glu	synonymous	Exon 8 of 9	ENSP00000476480.2	X6RM59
	NT5C3A	ENST00000456458.5	TSL:1	n.*766G>A		non_coding_transcript_exon	Exon 9 of 10	ENSP00000389676.2	F8WDR0
	NT5C3A	ENST00000456458.5	TSL:1	n.*766G>A		3_prime_UTR	Exon 9 of 10	ENSP00000389676.2	F8WDR0

Frequencies

GnomAD3 genomes AF: 0.00402 AC: 611 AN: 152178 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00495

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00671 AC: 1685 AN: 251248 AF XY: 0.00760

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00608

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.00452

Gnomad OTH exome AF: 0.00669

GnomAD4 exome AF: 0.00615 AC: 8965 AN: 1458216 Hom.: 77 Cov.: 28 AF XY: 0.00685 AC XY: 4973 AN XY: 725714

African (AFR) AF: 0.000838 AC: 28 AN: 33408

American (AMR) AF: 0.00606 AC: 271 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.000651 AC: 17 AN: 26114

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39666

South Asian (SAS) AF: 0.0286 AC: 2462 AN: 86098

European-Finnish (FIN) AF: 0.000711 AC: 38 AN: 53414

Middle Eastern (MID) AF: 0.00240 AC: 13 AN: 5418

European-Non Finnish (NFE) AF: 0.00519 AC: 5758 AN: 1109176

Other (OTH) AF: 0.00616 AC: 371 AN: 60220

GnomAD4 genome AF: 0.00403 AC: 614 AN: 152296 Hom.: 4 Cov.: 32 AF XY: 0.00440 AC XY: 328 AN XY: 74482

African (AFR) AF: 0.000818 AC: 34 AN: 41550

American (AMR) AF: 0.00490 AC: 75 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0302 AC: 146 AN: 4832

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00495 AC: 337 AN: 68022

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00414 Hom.: 0

Bravo AF: 0.00329

Asia WGS AF: 0.0190 AC: 66 AN: 3478

EpiCase AF: 0.00453

EpiControl AF: 0.00415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	2.9
DANN	Benign	0.61
PhyloP100		-0.045
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs72555746; hg19: chr7-33055315; COSMIC: COSV99641544; COSMIC: COSV99641544;